The proposed research program is designed to determine the physiological and structural substrates of action potential electrogenesis in an identified neuron and several identifiable classes of axons in a vertebrate central nervous system. The principal focus of the study will be the goldfish Mauthner cell, an identified reticulospinal cell. Using a combination of pharmacological and electrophysiological techniques, we will determine the extent to which voltage sensitive potassium channels influence action potential repolarization in the Mauthner cell's axon and in other central axons. Preliminary studies have indicated that the Mauthner cell axon hillock action potential includes, in addition to voltage sensitive sodium and potassium currents, a voltage sensitive calcium current. We will examine the effects on the Mauthner cell axon hillock action potential of other Ca++ antagonists and will study the regional distribution of these excitable channels in the axon and soma. Nodes of Ranvier have not been observed in the myelin sheath surrounding the Mauthner axon. Recent physiological evidence indicates that nodes, or "active sites" which are their functional equivalents, do occur along the Mauthner axon. We will attempt to identify these sites with standard morphological studies. In particular, we will electrophysiologically locate "active sites" along the Mauthner axon, mark the region using intracellular dyes of limited mobility and examine the region with light and electron microscopy. The morphology and spacing of these "active sites" will be compared to those of adjacent flm fibers and to nodes of Ranvier in peripheral axons of amphibians and mammals. Similar morphological and physiological studies on the Mauthner axon of younger fish will elucidate the relationships between conduction velocity, axon diameter, active site separation and membrane excitability properties. Pharmacological attempts to restore impulse conduction in demyelinating pathologies have been of limited success, possibly because the excitability properties of vertebrate axons have been inferred from limited experimental models. The proposed study will provide direct information on the properties of central vertebrate axons and is relevant to demyelinating diseases and drug treatment.